First attempts to restore the immunity system in primary and secondary immunodeficiency states have been made by way of transplantation of embryonal or neonatal thymus, and thymus in combination with sternum (cf. Yu. M. Lopukhin, Yu. I. Morozov, R. V. Petrov "Actual Problems of Transplantation of Organs", Moscow, 1974, pp. 286-302). In patients suffering from ataxia-telangiectasia (Louis-Bar syndrome), a genetic disease associated with disturbance of the function of T-cells in absence of immunoglobulins A and E (IgA, AgE), the transplantation of thymus causes a partial restoration of immunocompetence and a positive clinical dynamics. However, along with the tissue of the implanted thymus, numerous biochemical compounds are introduced into the body and a portion thereof can be toxic for the recipient. Insufficient vascularization, origination of immunological conflict are responsible for a rapid deterioration of the transplant. In transplantation of thymus it is impossible to ensure dosage of the active principle into the patient's organism. For this reason, the therapeutic effect in transplantation of thymus is but a short-termed and not always clearly pronounced. All these factors necessitate the production of preparations from thymus, or from other organs which should possess a considerably higher biological activity, a wide range of the therapeutic effect relative to primary and secondary immunodeficiency states caused by various external factors, malignant neoplasms having no immunogenic properties and causing no complications upon administration.
In the investigation of the preparation produced from thymus it has been found that its biological activity is due to the protein with the molecular mass of 12,600 Dalton. The method for producing the preparation involves homogenization of the tissue of thymus gland in NaCl, the removal of a residue from the homogenate, separation of thermolabile proteins from the solution, precipitation of proteins and peptides from the solution, dissolution of the precipitated proteins and peptides, salting-out of the peptides, dissolution of the residue of peptides, desalting of the separated peptides and lyophilization thereof (cf. Goldstein A. L., Guha A., et al., Proc. Natl. Acad. Sci. USA, 69, p.1800, 1972).
Further investigations have shown that the protein comprises an aggregation consisting of a number of polypeptides with a molecular mass of below 1,000 Dalton (cf. Hopper J. A., McDaniel M. C., et al., Ann. N.Y. Acad. Sci., 249, p.125, 1975).
Disk-electrophoresis in a polyacrylamide gel and isoelectric focusing in ampholines have made it possible to identify individual polypeptides. The biologically active fraction of thymosin (V fraction) has more than 20 components with a molecular mass of from 1,000 to 15,000 Dalton. It should be noted that certain polypeptide fractions of the preparation of thymus or combinations thereof have different biological activity in immunological tests in vivo and in vitro. Thus, the highest activity in the test of inhibition of migration of lymphocytes is manifested by .alpha.-thymosin with the molecular mass of 3,108 and pI of 4.2 (cf. Low, T. L. K., Goldstein A. L. In: The Year in Hematology; R. Silber, J. Lobuc, A. S. Gordon, eds) pp. 281-319, Plenum Publishing, New York, 1978). Other peptides produced from thymus, e.g. .beta..sub.3 and .beta..sub.4 induce the synthesis of the termonal desoxynucleotidyltransferase in precursors of T-cells. A number of polypeptides of thymus such as .beta..sub.1 are fully identical with biologically active peptides of other organs and, in particular, ubiquitin (cf. U.S. Pat. No. 4,002,602, 1977). Ubiquitin is capable of causing expression of T and B cell markers in vitro by activation of the adenylatecyclase cycle and influencing on .beta.-adrenergic receptors.
Also known is a thymic humoral factor capable of inducing immunocompetent cells in vitro by sensitivity of rosette-forming cells (E-RFC) in respect of azotioprin. The molecular mass of the humoral factor is about 56,700 Dalton; in fractions with a lower molecular mass there have been found only traces of biological activity (cf. White A. In: Biochemical Action of Hormones (G. Lidruk, ed.), Vol. 7, Academic Press, N.Y., 1979).
Therefore, thymus peptides, polypeptides and proteins have a too wide heterogeneity both in molecule size and biological properties thereof. It is obvious that a medical preparation based on peptides and possessing an effective action should contain molecules with a specific molecular mass and a sufficiently high biological activity. In this case a unique composition of peptides defines the range and efficiency of their therapeutic effect. The biological activity of peptides can be enhanced in principle by way of an additional purification, or by their chemical or enzymatic modification. The attempts of clinical application of the preparations containing polypeptides for stimulation of the T-system of immunity have been undertaken on patients suffering from primary and secondary immunodeficient states. In the case of the primary immunodeficient state (thymus hypoplasia) after the administration of a preparation containing thymus polypeptides the patient's condition is improved. However, directly after completion of the course of immunotherapy the patient's condition is sharply declined (cf. Goldstein A. L. et al., Transplant. Proc., V.7, pp. 681-686, 1975).
In secondary immunodeficient states caused by malignant tumors, the administration of the preparation containing polypeptides (V-fraction of thymus) has given a positive effect only in 5 patients out of 32 leukemia-suffering patients. In a patient with chorion-epithelioma the health condition is worsened (cf. Shafer L. A. et al., Ann. N.Y. Acad. Sci., V.277, pp.609-620, 1976). It should be noted that the preparation containing polypeptides (fraction V) has been administered in very high doses of about 400 mg/m.sup.2 per day for the period of 21 days. In patients with severe combined immunodeficiency no positive dynamics in the immunological status was observed at all. (Cf. Astaldi A. et al., Treat. Rep. 62, p.1779, 1978).
Therefore, it is an urgent medical problem to provide a preparation containing polypeptides which would be more effective in respect of primary and secondary immunodeficiency.